The objectives of this project are to characterize the biochemical and genetical mechanisms of obligate intracellular parasitism between the eukaryotic host and prokaryotic parasite. Molecular interactions at the cell surface and with soluble components are being investigated as primary determinants of metabolic cooperation between host and parasite. Rickettsia typhi utilize host purine nucleotides and in the absence of glutamate, adenosine 5'-triphosphate (ATP) is catabolized to AMP, the end product of ATP catabolism. Therefore, unusual membrane functions contribute to the success of the parasite as a scavenger of critical host components. Metabolic comparisons between autonomously growing bacteria and rickettsiae have revealed exploitable differences in antibiotic sensitivities. A cell wall directed antibiotic has been found which inhibits the growth of R. rickettssii but not Coxiella burnetii or R. typhi. Furthermore, this antibiotic restricts the growth of Rochalimaea quintana and Legionella pneumophila at an ED50 of 5 and 12 micro grams per ml, respectively.